Targeted disruption of Gdi2 causes early embryonic lethality

GDI2 regulates the GDP/GTP exchange reaction of Rab proteins by inhibiting the dissociation of GDP and the subsequent binding of GTP, dysregulation of GDI2 has been reported in many different cancers. Recently, we found that GDI2 bound to the ITIM domain of Siglec-G under normal homeostasis, whereas Rab1a was recruited to the ITIM domain during bacterial infection. Therefore, GDI2 and Rab1a may regulate the immune response through interaction with the ITIM domain during bacterial infection. However, the regulation of the inflammatory response by GDI2 in vivo and its regulatory mechanism remain unknown.

We generated a Gdi2 null mutant mouse with a trapped Gdi2 gene and examined the expression by X-gal and immunohistochemistry staining. TUNEL staining was used to determine the apoptosis cells.

Here we show that Gdi2 is essential for embryonic development. One functional Gdi2 allele is sufficient for murine embryo development, but complete loss of Gdi2 leads to embryonic lethality. Developmental retardation of Gdi2^-/- mice is apparent at E10.5 to E14.5, with no viable Gdi2^-/- embryos detected after E14.5. Histological analysis revealed extensive cell death and cell loss in Gdi2^-/- embryos. Apoptosis was confirmed by staining with cleaved caspase-3, suggesting that Gdi2 maintain homeostasis by regulating the apoptosis of the cells. There was no significant difference in cytokine production and survival between wild-type and Gdi2^+/- mice after LPS challenge.

These findings suggest that one Gdi2 allele is sufficient to maintain function. However, the detailed molecular mechanism underlying Gdi2 in regulating the embryonic development needs further identification.